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Philip Morris

the Solubility Loop of Nicotine: Water

Date: Jul 1994 (est.)
Length: 11 pages
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Davies, S.A.
Edwards
Gillard, R.D.
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Stmn/R2-038
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Glasstone
Hudson
Raoult
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2028341473/2028341563/Correspondence Outside
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2028341493/1504

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Univ of Wales Cardiff
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ILLE, ILLEGIBLE
MARG, MARGINALIA
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05 Jun 1998
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xnx85e00

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25 0 -75 v---~ 7% Mcotine o----Et 3% McoFine o------- 0 1% Nicotine l -100 ' - 220 240 260 280 Waveiength (nm) 300
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1994- 7-22 12:14 P.02 T0: 41 38 312 476 MROM:UWCC. CHEMY.CARDIFF ~ ~ P'I ~ ~ ~ 0 ~ ~ /I M '149.m °6 0 amqaa'&r %00i
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FROM-UWCC. CHEMY.CARDIFF TO: 41 38 312 476 1994- 7-22 12:13 P.01
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2028341497 ,- , ,;
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The Solubility Loop of Nicotine:Water Nicola S.A. Davies (n6e Edwards) and R.D. Gillard* lnurganic Chentistry Research Laboratory University of Wales, Cardiff P.O. Box 912, Cardiff CPl 3TB. 'I'hc lower consolute temperature in the nicotine:water system arises from the equilibrium formation of a covalent hydrate, revealcd by its unique circular dichroism. f Z0'd Oi:Zt ZZ-L -ti66T 9Gb ZT£ 8£ Tb :01 ddIQ21ti0'AW3H0 'JJmIl:W021d
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Nieotine([) is the major alkaloid of tobacco, from Nievtittiana tabacum : among its famous properties is the closed solubility loop in water, establishecll by Hudson. The version from Glasstone2 is reproduccd as Fig. 1. We have checked a few points on it in this work. The existence of lower consolute temperatures in binary mixtures has often been attributcd to the formation of a compound between the two components. We now show for nicotinc:water that this compound (lI) has its own spectroscopic properties distinct from those of nicotine (t). Fig. 2 shows the circular dichroism of solutions of natural nicotine in water at 400C, and Table l swnmarises rclated results. Typically, the spectra of the 1% solutions differ sharply from those of the 7% solutions. The source of the new properties is the covalent hydrate (11), as in (1). First, the most dilute solution (1%) shows a maximum Cotton effect at an energy about the same as that of the n-4 n* band in the vapour. This is no solvent effect on parent nicotine (I): those shift its c.d. to higher energies. In particular, more polar and hydrogen-bonding solvents lead to markcd blue shifts of n-+ tc* bands. Secondly, with change of condition, as in Fig. 2, the negative Cotton effect at 273nm gives place to another, centred at 26inm; a new positive Cotton effect at U 235nm also devclops. The c.d. of (I) has a negative Cotton effect, (n -+ n*), at longer wavelength and a positive Cotton effect, (n -4 ic*), at shortcr wavelength. O The negative one occurs at ca 273ntn (vapour and cyclohexane). Both shift to lower wavelengths in more polar environments (in weak -~ t U-3M - solution in water at 261 and 234nm). The c.d. of (II) shows no ~ rl~ it -a n* band, and a hand originating from the non-bonded N(n) electrons ~ at wavelengths from 272nm. Dilute (1%) aqueous solutions contain 'q, P-0'd eT:ZZ zZ-L -b66T 9Lb ZiE 8E Zb :01 ddIQdHJ'AW3HJ JOI~f1:W021d
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2 almost pure(II), weak (e.g. 10-3M) solutions of water in nicotine almost all(I). (1) The band at 2Gl nm has vibrational structure (Av = 850 ± 50 cm-t). The vapour and cyclohexane c.d. spectra also show vibrational structure (poorly resolved but of a similar progression). This structured band centred at 2binm is clearly the n-> zc* band of the pyridine chromophore of parent nicotine itself (i.e. I), in aqueous solution. This c.d. spectrum is essentially that reportcd several times4 and used analytically for much weaker solutions (around 10'2M or less) of natural nicotine in water at ambient temperatures. - Finally, the circular dichroism spectra of the three phases on the classical diagram (Nig. 1) can be assigned: (1) outside the loop: this phase has the band at 273nm which arises from the covalent --~ hydrate (II); (2) those of the conjugate phases inside the loop, (a) of nicotine (1) in nicotine (i) as solvent, containing water, (b) of nicotine(1) in water as solvent, with the c.d. like Band 2 in Fig. 2 The variation of c.d. with temperature and molar proportion is consistent with this explanation. As the region of immiscibility (the loop) is approached from outside, so the covalent hydrate band b0'd OT:Zi ZZ-G -b66t 9Gb Zi£ 8E tb :01 ~~IQ21tJ0'~lW3Fi0 OJI*I(1:W021=i
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3 disappears. At higher temperatures (z 70°C), the c.d. spectrum of nicotine (I) shows new bands, not represented on Fig. 2. In the coordinated nicotine of trans-[Ith(nic)4Cl2)+ ions, a very similar changc5 with increasing pH (disappearing band at 260nm, with a new negative Cotton effcct at 275nm) may well arise from the formation of a yr-base, rather than its conjugate acid seen here. 'fhc present observation is reminiscent of the finding3 that the vapour pressure (albeit at 25°C) of nicotine in its mixtures with water initially rises very sharply, over the mole fraction range 0-0.015 (i.e. -- 12%) then levels off to obey Raoult's law. Mixing the liquids causes evolution of heat and a marked change of volume. The presence of a covalent hydrate in aqueous solutions of natut•al nicotine is possibly relevant to its pharmacology and toxicity. t~ Some Z dilute solutions at physiological temperatures (ca 370C) are, indeed, doniinated by the nan-arornatic spe` ies. Mixtures of other N- heterocycles with water also manifest similar closed solubility loops with lower consolute ternperatures6 ([3-picoline at 490, 2,6-lutidine at 1 440) presu~ly also vi,a a covalent hydrate (nicotine of course being a derivative of 3-methyl pyridine). The equilibrium involving c'bvalent hydration of the N-hetcrocyclic solvent may help to account for the well-known revcrsal7,8 of energy and intensity for the visible absorptions of some cyanine dyes in water:pyridine mixtures, where typically the dyestuff in pure pyridine shows first a red shift on diluting with water, which on further dilution reverses into a blue shift. The abrupt rise in vapour pressure of nicotine in its dilute solutions in ~ water is indeed closely mimicked by pyridine:water9. ~ The covalent hydrate ([I) contains new elements of chirality: a 1 ~ new "sp3-hybridized" carbon atom, an as mmetric ' nitro en atom, and ~ possibly a skewed dienc system. The isomcric j structure of (Il) and the CA l IT ~ , S0' d i T: Z i ZZ-L -b66i 9Lb ZZE 9E tti :01 dd QHti0 ' hW3H0 ' OJ~ill : W02id
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r degree of stereoselective induction in its formation from ~ be established. (1) remain to lteferences 1. C.S. Hudson, Zeit. Phys. Chem., 1904, gZ, 113. 2. S. Glasstone, "Textbook of Physical Chemistry", British re-issue of 2nd Ed., 1951, p. 728, Macmillan, London: also given in V.B. John, "Understanding Phase Diagrams", p.30, Macmillan, London, 1974. 3. L.I3. Norton, C'.IZ. Bigelow and N.13. Vinccnt, .l. Amer. Chein. Soc.. 1940, C2, 261. 4(a) W.M. Atkinson, S.M. Han and N. Purdie, Anal. Chem., 1984, 5A, 1947; (this in methanolic KOH, with concentrations <10-3M). (b) A. Tomita, I's-l. Uchiai, 1-I. Hirai and S. Makishima, J. Inorg. Nucl. 5. Chent., 1967, 22, 105 (this in 95% alcohol at 170C). R.D. Gillard antl J.l'. de Jesus, Croat. Chim. Acta, 1989, U, 1.51. W~"- 6. G. Cox, J. Chem. Soc., 1909, 91, 668 (the values given are estimated 7. by re-plotting Cox's results: the full loops are in the Ph.D. thesis of N.S.A. Edwards, Univ. of Wales, 1994). J.N. Murrell, 'The Theory of the Electronic Spectra of Organic , 8. Molecules', Methucn, 1963, p. 87. L.G.S. Brooker, G.H. Keyes and D.W. Heseltine, J. Amer. Chem. Soc., 1951, 7a, 5350. 9. J. Zawidzki, Zcit. Phys. Chem., 1900, 31, 129. 4 90'd Ii:Zt ZZ-G -b66t 9Lb ZTE 8E Tb :01 ddIQ21Fi0'~1W3H0 '001'If1:W021d
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5 Table 1. Circular Uichroisrn of Nicotine: Water Mixtures Condition T(«C) ~ sign sign sign Comment Vapour 5 273 - 245 + Unsolvated 20 274 - 245 + monomer([) 40 274 - 245 + Cyclohexanea 268 -2.31 244 +1.14 (1) solvated by cyclohexane 1% Nicotine: 30 273 - Chiefly H20b covalent hydrate(II) 3% Nicotine: 30 272, - 234 + (11), decreasing H20 c,d 261 - with increasing proportion of 5% Nicotine: 3 0 273, - 234 + (I) solvated by H20 c.e 261 - H20 r / a. Sodiutn-dricd. b. No distinct hands observed at lower wavelengths. AE273: AE26t = 10. c. In these mixtures, Cotton effects appeared at 261(-) and 234(+): d. AE273: AE261 = 2.1; AE27;t: AE234 = 0.15. e. AE273: AE261 = 1.1; DE273: AE234 = 0.26 N O N ~ 1N+ O LJ L0'd ZZ:ZZ ZZ-L -b66T 90 ZTE 8£ Iti :01 ddIQ21d0'1,W3H0 'J01*I(1:W021d

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